한빛사논문
- 조회1,408
Salvatore Lorenzo Renne1,*, Ha Young Woo2,*, Sarah Allegra1*, Noemi Rudini1, Hirohisa Yano3, Matteo Donadon4,5, Luca Viganò4,5, Jun Akiba6, Hye Sun Lee7, Hyungjin Rhee8, Young Nyun Park2,§ ,Massimo Roncalli1,5,§ , Luca Di Tommaso1,5
* SLR, HYW, SA equally contributed as first authors.
1 Department of Pathology, Humanitas Clinical and Research Center – IRCCS, Rozzano (MI) Italy
2 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
3 Department of Pathology, Kurume University School of Medicine, Kurume, Japan
4 Department of Hepatobiliary Surgery, Humanitas Clinical and Research Center – IRCCS, Rozzano (MI), Italy
§ Corresponding authors: Massimo Roncalli, Young Nyun Park
Abstract
We investigated the clinical significance of a vascular growth pattern of hepatocellular carcinoma (HCC), the VETC (vessels that encapsulate tumor clusters), previously linked to HCC metastatic dissemination. VETC was assessed in a large multi‐institutional cohort of 541 resected HCCs from Italy, Korea and Japan, and matched against a full spectrum of clinical and pathological variables. The VETC phenotype (defined as ≥55% tumor area by CD34 immunostaining) was easily reproducible and reliably detectable in whole sections and small sized tissues of tissue microarray. VETC‐HCCs represented the 18.9% of the whole series, the lowest proportion occurring in the cohort with smallest tumors (8.7%, Japanese series). VETC was significantly associated to several clinical and pathological features such as: high AFP level, tumor size >5 cm, poor differentiation, macrotrabecular pattern, less compact pattern, less inflammatory infiltrates, and frequent microvascular invasion. VETC was associated with early recurrence [HR: 1.52 (1.06‐2.19), p= 0.023], DFS [HR: 1.66 (1.21‐2.27), p= 0.002] and OS [HR: 2.26 (1.37‐3.72), p= 0.001] at multivariable analysis. VETC impacted on survival in HCC patients stratified for etiology (HCV/HBV), vascular invasion and specific molecular phenotypes (β‐catenin/GS+). This distinct vascular pattern was enriched in the recently reported macro‐trabecular massive HCC subtype, which was seen in 7.8% (42/541) and associated with high AFP levels, poor differentiation. In conclusion, the VETC pattern revealed to be easily detectable in a consistent fraction of HCC and to be a powerful pathological finding impacting on survival. This study suggests that the heterogeneous pattern of angiogenesis is involved in HCC behavior.
Keywords : HCC vascular microenvironment, tumor pattern, VETC, macrotrabecular massive, prognosis
논문정보
- Research article
- 2019년 06월 (BRIC 등록일 2019-06-26)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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